A compound labeled with an isotope is useful to examine in vivo kinetics of drug, in particular, a compound labeled with deuterium (D) is generally utilized for this purpose.
The compound labeled with deuterium has generally been synthesized by a conventional method using a preliminary deuterated starting material, however, said synthetic method has a problem with requiring multiple synthetic steps, so it is desired to develop a method for obtaining a compound labeled with deuterium by directly exchanging C—H of a final objective compound for C-D (H-D exchange).
The present inventors have conducted extensive study and have found a method for selective deuteration of only a hydrogen atom binded to a carbon atom directly bonded to an aromatic ring (a hydrogen atom at the benzyl position). However, said deuteration method provides still low deuteration rate of a hydrogen atom at terminal carbon even at benzyl position (a hydrogen atom of a methyl group directly bonded to an aromatic ring) and no deuteration of a hydrogen atom bonded to-a carbon atom other than at benzyl position. Therefore, it has been desired to develop a method for attaining high deuteration rate of a hydrogen atom of a methyl group directly bonded to an aromatic ring and also deuteration of a hydrogen atom bonded to a carbon atom other than at benzyl position.
Therefore, the purpose of the present invention is to develop a method for high deuteration rate of a hydrogen atom in a methyl group directly bonded to an aromatic ring and also an effective deuteration of not only a hydrogen atom at benzyl position but also a hydrogen atom bonded to the other carbon atoms.